GH MODULATION OF EGF-INDUCED PI3K-AKT SIGNAL IN MOUSE LIVER

MA. EUGENIA DÍAZ; LORENA GONZÁLEZ; JOHANNA G MIQUET; CAROLINA S MARTÍNEZ; ANA I SOTELO; DANIEL TURYN

Congreso; The First South American Spring Symposium in Signal Transduction and Molecular Medicine (SISTAM).; 2010

CONICET

Epidermal growth factor receptor (EGFR) and growth hormone (GH) have been related to hepatocellular carcinoma development. Taking into account that the PI3K-Akt pathway is involved in tumorogenesis and the EGFR is transactivated by GH, the GH modulation of EGF-induced PI3K-Akt pathway was studied in liver. With this purpose, protein content and phosphorylation levels of PI3K-Akt pathway mediators were studied in the liver of transgenic mice that overexpress GH and in their normal siblings.Transgenic mice had a diminished response to EGF stimulation: Akt activation was reduced and its substrates, GSK3 and mTOR, were not phosphorylated even when they were overexpressed. This desensitization was not associated to diminished activity of PDK1, a kinase involved in Akt activation, or to hyperactivation of PTEN, a phosphatase involved in PI3K-Akt pathway inhibition. In contrast, overexpressed GH was associated with the reduction of Gab1 levels, a docking protein that allows PI3K activation, which might explain the decreased EGF-induction of the PI3K-Akt pathway. Moreover, increased SHP2 in membranes from transgenic mice and association of this phosphatase to Gab1 could result in the reduced activation of Akt observed in the transgenic mice.